Breast Cancer Vaccines Look Promising

By Kathleen Doheny
27 JUNE 2008-- Women with metastatic breast cancer who developed an immune response to an investigational vaccine lived twice as long as those who didn't have an immune response, new research shows.
"If you were an immune responder, you had double the survival of a non-responder," said study author Dr. Susan Domchek, an associate professor of medicine at the University of Pennsylvania.
Her report is one of several focusing on breast cancer vaccines expected to be discussed this week at the Department of Defense Era of Hope breast cancer research meeting, in Baltimore.
"Metastatic breast cancer is treatable but not curable," Domchek said. While the ultimate hope is to cure the cancer, breast cancer vaccines are one possible way to try to control the disease's spread.
Although most people think of vaccines as shots given to healthy people to prevent infectious diseases such as measles and the flu, various cancer vaccines that have been studied for decades use cancer cells, parts of cells or substances called antigens to trigger an immune response against cancer cells already in the body.
In her study, Domchek used pieces of a protein called human telomerase reverse transcriptase (hTERT) peptide to vaccinate 19 women with breast cancer that had spread. The peptide is nearly universally overexpressed in human cancers and is recognized by certain T-cells in the body's immune system.
At the start of the study, the women had no measurable T-cell response to hTERT. After up to eight vaccinations with the hTERT peptide, however, 13 of the 19 women made T-cells that reacted to the peptide.
"We biopsied the patients' breast cancer and saw that we could see these T-cells in the tumors themselves," she said. "And, in some cases, we could see evidence of tumor cells' death."
"Those who responded lived significantly longer," she said. "People who responded lived 32 months versus a median of 17 [for those who did not respond]. Three of the women who were responders have lived more than three years."
Among the questions that remain, however, said Domchek, is this: "Were those women going to do well no matter what we did? Is immune response just a marker for a healthier patient?"
Other research on breast cancer vaccines expected to be presented at the meeting include:A study that focused on breast cancer patients with HER-2-positive tumors (for whom relapse is common after treatment) treated with a combination of vaccine plus an anti-cancer drug. Dr. Lupe Salazar, an assistant professor of medicine at the University of Washington, in Seattle, and her team sequenced the HER-2 protein and put pieces of it into a vaccine. They gave it to patients, along with the anti-cancer drug Herceptin. The combination helped to generate significant levels of T-cell immunity specific to the HER-2 cells, she said. As of now, "all eight [women] have done this," she said. The study will eventually include 52 women. A study that uses immunostimulatory peptides as a vaccine looked at the best way to deliver them. Dr. Davorka Messmer, an assistant project scientist at the Moores Cancer Center at the University of California San Diego, and her team tested a vaccine using nanoparticles loaded with the HER2 peptide that carry an immune system-stimulating peptide, called Hp91, on the outside or the inside. "We found it more potent if the immunostimulatory peptide was put on the surface of the nanoparticle," she said. The study was conducted in animals.
While breast cancer vaccines have been studied for at least 30 years, they have yet to make a real difference in the lives of patients, said Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. That's not to say they won't someday, he added.
"When you look at the theory, it makes sense," he said. "The bottom line is, we are getting there, but [we're] not there yet."
Many questions remain, he said, such as "why some patients have immune responses, and others don't." It is likely, he said, that some of the vaccines will be specific to one cancer, and others may work on more than one type of cancer.